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Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneuro...

Rodrigues, Rui S.; Moreira, João B.; Mateus, Joana; Barateiro, Andreia; Paulo, Sara L; Vaz, Sandra H.; Lourenço, Diogo M.; Ribeiro, Filipa; Soares, Rita

Chronic stress is a major risk factor for neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important ef...


Unravelling a novel role for cannabidivarin in the modulation of subventricular...

Lourenço, Diogo M.; Soares, Rita; Sá Santos, Sónia; Mateus, Joana; Rodrigues, Rui S.; Moreira, João B.; Vaz, Sandra H.; Sebastião, Ana M; Solá, Susana

Postnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis. Using the neurosphere assay, SVZ-derived neural stem/progenitor cells (NSPCs) were incubated with CBDV and/or 5'-Iodore...


Sustained hippocampal neural plasticity questions the reproducibility of an amy...

Paulo, Sara L; Ribeiro Rodrigues, Leonor; Rodrigues, Rui S.; Mateus, Joana; Fonseca-Gomes, João; Soares, Rita; Diógenes, Maria José; Solá, Susana

Background: The use of Alzheimer's disease (AD) models obtained by intracerebral infusion of amyloid-β (Aβ) has been increasingly reported in recent years. Nonetheless, these models may present important challenges. Objective: We have focused on canonical mechanisms of hippocampal-related neural plasticity to characterize a rat model obtained by an intracerebroventricular (icv) injection of soluble amyloid-β42 ...


High-caloric diet Induces memory impairment and disrupts synaptic plasticity in...

Paulo, Sara L; Miranda-Lourenço, Catarina; Belo, Rita F.; Rodrigues, Rui S.; Fonseca-Gomes, João; Tanqueiro, Sara; Geraldes, Vera; Rocha, Isabel

The increasing consumption of sugar and fat seen over the last decades and the consequent overweight and obesity, were recently linked with a deleterious effect on cognition and synaptic function. A major question, which remains to be clarified, is whether obesity in the elderly is an additional risk factor for cognitive impairment. We aimed at unravelling the impact of a chronic high caloric diet (HCD) on memo...


Regulation of hippocampal postnatal and adult neurogenesis by adenosine A2A rec...

Ribeiro, Filipa; Ferreira, Filipa; Rodrigues, Rui S.; Soares, Rita; Pedro, Diogo; Duarte-Samartinho, Marta; Aroeira, Rita I.; Ferreiro, Elisabete

Adenosine A2A receptor (A2A R) activation modulates several brain processes, ranging from neuronal maturation to synaptic plasticity. Most of these actions occur through the modulation of the actions of the neurotrophin brain-derived neurotrophic factor (BDNF). In this work, we studied the role of A2A Rs in regulating postnatal and adult neurogenesis in the rat hippocampal dentate gyrus (DG). Here, we show that...


The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safe...

Santos, Sónia Sá; Moreira, João B.; Costa, Márcia; Rodrigues, Rui S.; Sebastião, Ana M; Xapelli, Sara; Solá, Susana

Neural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative protection, in the fate of NSC under aging and depression-like c...


The neurosphere assay : an effective in vitro technique to study neural stem cells

Xapelli, Sara; Soares, Rita; Ribeiro, Filipa; Lourenço, Diogo M.; Rodrigues, Rui S.; Moreira, João B.; Sebastião, Ana M.; Morais, Vanessa A.

Neural stem cells (NSCs) are known to be present in the adult mammalian brain where they constitutively differentiate into the neuronal, astroglial, and oligodendroglial lineages, in defined processes termed n e u ro ge n e s i s , a st ro g l i o ge n e s i s a n d oligodendrogenesis, respectively (reviewed in Braun and Jessberger, 2014). During brain development, NSCs are present throughout the brain, becomin...


Cannabinoid actions on neural stem cells: implications for pathophysiology

Rodrigues, Rui S.; Lourenço, Diogo M.; Paulo, Sara L; Mateus, Joana; Ferreira, Miguel F.; Mouro, Francisco; Moreira, João B.; Ribeiro, Filipa

With the increase of life expectancy, neurodegenerative disorders are becoming not only a health but also a social burden worldwide. However, due to the multitude of pathophysiological disease states, current treatments fail to meet the desired outcomes. Therefore, there is a need for new therapeutic strategies focusing on more integrated, personalized and effective approaches. The prospect of using neural stem...


Brain-derived neurotrophic factor (BDNF) role in cannabinoid-mediated neurogenesis

Ferreira, Filipa Fiel; Ribeiro, Filipa; Rodrigues, Rui S.; Sebastião, Ana M; Xapelli, Sara

The adult mammalian brain can produce new neurons in a process called adult neurogenesis, which occurs mainly in the subventricular zone (SVZ) and in the hippocampal dentate gyrus (DG). Brain-derived neurotrophic factor (BDNF) signaling and cannabinoid type 1 and 2 receptors (CB1R and CB2R) have been shown to independently modulate neurogenesis, but how they may interact is unknown. We now used SVZ and DG neuro...


Interaction between cannabinoid type 1 and type 2 receptors in the modulation o...

Rodrigues, Rui S.; Ribeiro, Filipa; Ferreira, Filipa; Vaz, Sandra H.; Sebastião, Ana M; Xapelli, Sara

Neurogenesis in the adult mammalian brain occurs mainly in two neurogenic niches, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus (DG). Cannabinoid type 1 and 2 receptors (CB1R and CB2R) have been shown to differently modulate neurogenesis. However, low attention has been given to the interaction between CB1R and CB2R in modulating postnatal neurogenesis (proliferation, neurona...


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